GSK3B_HUMAN
ID GSK3B_HUMAN Reviewed; 420 AA.
AC P49841; D3DN89; Q9BWH3; Q9UL47;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 02-MAY-2002, sequence version 2.
DT 03-AUG-2022, entry version 256.
DE RecName: Full=Glycogen synthase kinase-3 beta;
DE Short=GSK-3 beta;
DE EC=2.7.11.26 {ECO:0000269|PubMed:14690523};
DE AltName: Full=Serine/threonine-protein kinase GSK3B;
DE EC=2.7.11.1 {ECO:0000269|PubMed:17050006, ECO:0000269|PubMed:22539723, ECO:0000269|PubMed:28992046};
GN Name=GSK3B;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND MUTAGENESIS OF SER-9.
RX PubMed=7980435; DOI=10.1042/bj3030701;
RA Stambolic V., Woodgett J.R.;
RT "Mitogen inactivation of glycogen synthase kinase-3 beta in intact cells
RT via serine 9 phosphorylation.";
RL Biochem. J. 303:701-704(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Eye, and Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-28.
RX PubMed=10486203; DOI=10.1006/geno.1999.5875;
RA Lau K.F., Miller C.C.J., Anderton B.H., Shaw P.C.;
RT "Molecular cloning and characterization of the human glycogen synthase
RT kinase-3beta promoter.";
RL Genomics 60:121-128(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 185-202.
RX PubMed=10523816; DOI=10.1038/sj.mp.4000538;
RA Rhoads A.R., Karkera J.D., Detera-Wadleigh S.D.;
RT "Radiation hybrid mapping of genes in the lithium-sensitive wnt signaling
RT pathway.";
RL Mol. Psychiatry 4:437-442(1999).
RN [6]
RP FUNCTION IN PHOSPHORYLATION OF JUN.
RX PubMed=1846781; DOI=10.1016/0092-8674(91)90241-p;
RA Boyle W.J., Smeal T., Defize L.H., Angel P., Woodgett J.R., Karin M.,
RA Hunter T.;
RT "Activation of protein kinase C decreases phosphorylation of c-Jun at sites
RT that negatively regulate its DNA-binding activity.";
RL Cell 64:573-584(1991).
RN [7]
RP FUNCTION IN PHOSPHORYLATION OF EIF2BE/EIF2B5.
RX PubMed=8397507; DOI=10.1042/bj2940625;
RA Welsh G.I., Proud C.G.;
RT "Glycogen synthase kinase-3 is rapidly inactivated in response to insulin
RT and phosphorylates eukaryotic initiation factor eIF-2B.";
RL Biochem. J. 294:625-629(1993).
RN [8]
RP PHOSPHORYLATION AT SER-9.
RX PubMed=8250835; DOI=10.1042/bj2960015;
RA Sutherland C., Leighton I.A., Cohen P.;
RT "Inactivation of glycogen synthase kinase-3 beta by phosphorylation: new
RT kinase connections in insulin and growth-factor signalling.";
RL Biochem. J. 296:15-19(1993).
RN [9]
RP ACTIVITY REGULATION BY AKT1.
RX PubMed=8524413; DOI=10.1038/378785a0;
RA Cross D.A., Alessi D.R., Cohen P., Andjelkovich M., Hemmings B.A.;
RT "Inhibition of glycogen synthase kinase-3 by insulin mediated by protein
RT kinase B.";
RL Nature 378:785-789(1995).
RN [10]
RP FUNCTION IN PHOSPHORYLATION OF NFATC1/NFATC.
RX PubMed=9072970; DOI=10.1126/science.275.5308.1930;
RA Beals C.R., Sheridan C.M., Turck C.W., Gardner P., Crabtree G.R.;
RT "Nuclear export of NF-ATc enhanced by glycogen synthase kinase-3.";
RL Science 275:1930-1934(1997).
RN [11]
RP INTERACTION WITH DNM1L.
RC TISSUE=Liver;
RX PubMed=9731200; DOI=10.1006/bbrc.1998.9253;
RA Hong Y.-R., Chen C.-H., Cheng D.-S., Howng S.-L., Chow C.-C.;
RT "Human dynamin-like protein interacts with the glycogen synthase kinase
RT 3beta.";
RL Biochem. Biophys. Res. Commun. 249:697-703(1998).
RN [12]
RP INTERACTION WITH MUC1, AND FUNCTION.
RX PubMed=9819408; DOI=10.1128/mcb.18.12.7216;
RA Li Y., Bharti A., Chen D., Gong J., Kufe D.;
RT "Interaction of glycogen synthase kinase 3beta with the DF3/MUC1 carcinoma-
RT associated antigen and beta-catenin.";
RL Mol. Cell. Biol. 18:7216-7224(1998).
RN [13]
RP CHARACTERIZATION.
RX PubMed=9736715; DOI=10.1073/pnas.95.19.11211;
RA Delcommenne M., Tan C., Gray V., Rue L., Woodgett J.R., Dedhar S.;
RT "Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase
RT kinase 3 and protein kinase B/AKT by the integrin-linked kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:11211-11216(1998).
RN [14]
RP INTERACTION WITH NIN.
RX PubMed=11004522; DOI=10.1016/s0167-4781(00)00127-5;
RA Hong Y.-R., Chen C.-H., Chang J.-H., Wang S.-K., Sy W.-D., Chou C.-K.,
RA Howng S.-L.;
RT "Cloning and characterization of a novel human ninein protein that
RT interacts with the glycogen synthase kinase 3beta.";
RL Biochim. Biophys. Acta 1492:513-516(2000).
RN [15]
RP ASSOCIATION WITH DIABETES MELLITUS.
RX PubMed=10868943; DOI=10.2337/diabetes.49.2.263;
RA Nikoulina S.E., Ciaraldi T.P., Mudaliar S., Mohideen P., Carter L.,
RA Henry R.R.;
RT "Potential role of glycogen synthase kinase-3 in skeletal muscle insulin
RT resistance of type 2 diabetes.";
RL Diabetes 49:263-271(2000).
RN [16]
RP FUNCTION, AND MUTAGENESIS OF ARG-96 AND LEU-128.
RX PubMed=11430833; DOI=10.1016/s1097-2765(01)00253-2;
RA Frame S., Cohen P., Biondi R.M.;
RT "A common phosphate binding site explains the unique substrate specificity
RT of GSK3 and its inactivation by phosphorylation.";
RL Mol. Cell 7:1321-1327(2001).
RN [17]
RP PHOSPHORYLATION AT SER-9 BY SGK3, AND INTERACTION WITH SGK3.
RX PubMed=12054501; DOI=10.1016/s0006-291x(02)00349-2;
RA Dai F., Yu L., He H., Chen Y., Yu J., Yang Y., Xu Y., Ling W., Zhao S.;
RT "Human serum and glucocorticoid-inducible kinase-like kinase (SGKL)
RT phosphorylates glycogen syntheses kinase 3 beta (GSK-3beta) at serine-9
RT through direct interaction.";
RL Biochem. Biophys. Res. Commun. 293:1191-1196(2002).
RN [18]
RP FUNCTION IN PHOSPHORYLATION OF MAPT/TAU.
RX PubMed=14690523; DOI=10.1111/j.1471-4159.2004.02155.x;
RA Cho J.H., Johnson G.V.;
RT "Primed phosphorylation of tau at Thr231 by glycogen synthase kinase 3beta
RT (GSK3beta) plays a critical role in regulating tau's ability to bind and
RT stabilize microtubules.";
RL J. Neurochem. 88:349-358(2004).
RN [19]
RP FUNCTION, INTERACTION WITH SNAI1, AND SUBCELLULAR LOCATION.
RX PubMed=15448698; DOI=10.1038/ncb1173;
RA Zhou B.P., Deng J., Xia W., Xu J., Li Y.M., Gunduz M., Hung M.C.;
RT "Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control
RT of epithelial-mesenchymal transition.";
RL Nat. Cell Biol. 6:931-940(2004).
RN [20]
RP INTERACTION WITH CABYR.
RX PubMed=15752768; DOI=10.1016/j.bbrc.2005.02.089;
RA Hsu H.-C., Lee Y.-L., Cheng T.-S., Howng S.-L., Chang L.-K., Lu P.-J.,
RA Hong Y.-R.;
RT "Characterization of two non-testis-specific CABYR variants that bind to
RT GSK3beta with a proline-rich extensin-like domain.";
RL Biochem. Biophys. Res. Commun. 329:1108-1117(2005).
RN [21]
RP FUNCTION, AND INTERACTION WITH SNAI1.
RX PubMed=15647282; DOI=10.1074/jbc.m413878200;
RA Yook J.I., Li X.Y., Ota I., Fearon E.R., Weiss S.J.;
RT "Wnt-dependent regulation of the E-cadherin repressor snail.";
RL J. Biol. Chem. 280:11740-11748(2005).
RN [22]
RP INTERACTION WITH GSKIP.
RX PubMed=16981698; DOI=10.1021/bi061147r;
RA Chou H.-Y., Howng S.-L., Cheng T.-S., Hsiao Y.-L., Lieu A.-S., Loh J.-K.,
RA Hwang S.-L., Lin C.-C., Hsu C.-M., Wang C., Lee C.-I., Lu P.-J.,
RA Chou C.-K., Huang C.-Y., Hong Y.-R.;
RT "GSKIP is homologous to the axin GSK3beta interaction domain and functions
RT as a negative regulator of GSK3beta.";
RL Biochemistry 45:11379-11389(2006).
RN [23]
RP INTERACTION WITH PRUNE1.
RX PubMed=16428445; DOI=10.1128/mcb.26.3.898-911.2006;
RA Kobayashi T., Hino S., Oue N., Asahara T., Zollo M., Yasui W., Kikuchi A.;
RT "Glycogen synthase kinase 3 and h-prune regulate cell migration by
RT modulating focal adhesions.";
RL Mol. Cell. Biol. 26:898-911(2006).
RN [24]
RP FUNCTION, AND PHOSPHORYLATION AT SER-9.
RX PubMed=16484495; DOI=10.1126/science.1121613;
RA Yin L., Wang J., Klein P.S., Lazar M.A.;
RT "Nuclear receptor Rev-erbalpha is a critical lithium-sensitive component of
RT the circadian clock.";
RL Science 311:1002-1005(2006).
RN [25]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF SER-9 AND 85-LYS-LYS-86.
RX PubMed=17050006; DOI=10.1016/j.bbamcr.2006.09.015;
RA Garcia-Alvarez G., Ventura V., Ros O., Aligue R., Gil J., Tauler A.;
RT "Glycogen synthase kinase-3beta binds to E2F1 and regulates its
RT transcriptional activity.";
RL Biochim. Biophys. Acta 1773:375-382(2007).
RN [26]
RP INTERACTION WITH AXIN1.
RX PubMed=17318175; DOI=10.1038/sj.emboj.7601607;
RA Luo W., Peterson A., Garcia B.A., Coombs G., Kofahl B., Heinrich R.,
RA Shabanowitz J., Hunt D.F., Yost H.J., Virshup D.M.;
RT "Protein phosphatase 1 regulates assembly and function of the beta-catenin
RT degradation complex.";
RL EMBO J. 26:1511-1521(2007).
RN [27]
RP FUNCTION, AND INTERACTION WITH BIRC2; DDX3X AND TNFRSF10B.
RX PubMed=18846110; DOI=10.1038/cdd.2008.124;
RA Sun M., Song L., Li Y., Zhou T., Jope R.S.;
RT "Identification of an antiapoptotic protein complex at death receptors.";
RL Cell Death Differ. 15:1887-1900(2008).
RN [28]
RP FUNCTION IN PHOSPHORYLATION OF SIK1.
RX PubMed=18348280; DOI=10.1002/jcb.21737;
RA Hashimoto Y.K., Satoh T., Okamoto M., Takemori H.;
RT "Importance of autophosphorylation at Ser186 in the A-loop of salt
RT inducible kinase 1 for its sustained kinase activity.";
RL J. Cell. Biochem. 104:1724-1739(2008).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-402, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-390, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [31]
RP INTERACTION WITH MMP2.
RX PubMed=19493954; DOI=10.1093/cvr/cvp175;
RA Kandasamy A.D., Schulz R.;
RT "Glycogen synthase kinase-3beta is activated by matrix metalloproteinase-2
RT mediated proteolysis in cardiomyoblasts.";
RL Cardiovasc. Res. 83:698-706(2009).
RN [32]
RP FUNCTION, AND INTERACTION WITH CLOCK-ARNTL/BMAL1.
RX PubMed=19946213; DOI=10.4161/cc.8.24.10273;
RA Spengler M.L., Kuropatwinski K.K., Schumer M., Antoch M.P.;
RT "A serine cluster mediates BMAL1-dependent CLOCK phosphorylation and
RT degradation.";
RL Cell Cycle 8:4138-4146(2009).
RN [33]
RP INTERACTION WITH CTNND2.
RX PubMed=19706605; DOI=10.1074/jbc.m109.002659;
RA Oh M., Kim H., Yang I., Park J.H., Cong W.T., Baek M.C., Bareiss S., Ki H.,
RA Lu Q., No J., Kwon I., Choi J.K., Kim K.;
RT "GSK-3 phosphorylates delta-catenin and negatively regulates its stability
RT via ubiquitination/proteosome-mediated proteolysis.";
RL J. Biol. Chem. 284:28579-28589(2009).
RN [34]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [35]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [36]
RP FUNCTION, AND ALTERNATIVE SPLICING.
RX PubMed=20067585; DOI=10.1111/j.1471-4159.2010.06581.x;
RA Castano Z., Gordon-Weeks P.R., Kypta R.M.;
RT "The neuron-specific isoform of glycogen synthase kinase-3beta is required
RT for axon growth.";
RL J. Neurochem. 113:117-130(2010).
RN [37]
RP FUNCTION.
RX PubMed=20932480; DOI=10.1016/j.molcel.2010.09.013;
RA Heyd F., Lynch K.W.;
RT "Phosphorylation-dependent regulation of PSF by GSK3 controls CD45
RT alternative splicing.";
RL Mol. Cell 40:126-137(2010).
RN [38]
RP INTERACTION WITH DAB2IP AND PPP2CA.
RX PubMed=20080667; DOI=10.1073/pnas.0908133107;
RA Xie D., Gore C., Liu J., Pong R.C., Mason R., Hao G., Long M., Kabbani W.,
RA Yu L., Zhang H., Chen H., Sun X., Boothman D.A., Min W., Hsieh J.T.;
RT "Role of DAB2IP in modulating epithelial-to-mesenchymal transition and
RT prostate cancer metastasis.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:2485-2490(2010).
RN [39]
RP FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT SER-9.
RX PubMed=20937854; DOI=10.1073/pnas.1000975107;
RA Zaoui K., Benseddik K., Daou P., Salaun D., Badache A.;
RT "ErbB2 receptor controls microtubule capture by recruiting ACF7 to the
RT plasma membrane of migrating cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:18517-18522(2010).
RN [40]
RP REVIEW ON FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=11749387; DOI=10.1021/cr000110o;
RA Ali A., Hoeflich K.P., Woodgett J.R.;
RT "Glycogen synthase kinase-3: properties, functions, and regulation.";
RL Chem. Rev. 101:2527-2540(2001).
RN [41]
RP REVIEW ON FUNCTION.
RX PubMed=17478001; DOI=10.1016/j.diabres.2007.01.033;
RA Lee J., Kim M.S.;
RT "The role of GSK3 in glucose homeostasis and the development of insulin
RT resistance.";
RL Diabetes Res. Clin. Pract. 77:S49-S57(2007).
RN [42]
RP REVIEW ON FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=19366350; DOI=10.1111/j.1476-5381.2008.00085.x;
RA Rayasam G.V., Tulasi V.K., Sodhi R., Davis J.A., Ray A.;
RT "Glycogen synthase kinase 3: more than a namesake.";
RL Br. J. Pharmacol. 156:885-898(2009).
RN [43]
RP INTERACTION WITH GSKIP, AND COMPLEX FORMATION WITH PRKAR2A AND GSKIP.
RX PubMed=20007971; DOI=10.1074/jbc.m109.047944;
RA Hundsrucker C., Skroblin P., Christian F., Zenn H.M., Popara V., Joshi M.,
RA Eichhorst J., Wiesner B., Herberg F.W., Reif B., Rosenthal W.,
RA Klussmann E.;
RT "Glycogen synthase kinase 3beta interaction protein functions as an A-
RT kinase anchoring protein.";
RL J. Biol. Chem. 285:5507-5521(2010).
RN [44]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [45]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [46]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND PHOSPHORYLATION.
RX PubMed=21029237; DOI=10.1111/j.1750-3639.2010.00437.x;
RA Bose A., Mouton-Liger F., Paquet C., Mazot P., Vigny M., Gray F., Hugon J.;
RT "Modulation of tau phosphorylation by the kinase PKR: implications in
RT Alzheimer's disease.";
RL Brain Pathol. 21:189-200(2011).
RN [47]
RP FUNCTION.
RX PubMed=22514281; DOI=10.1074/jbc.m111.306373;
RA Sun L., Lv F., Guo X., Gao G.;
RT "Glycogen synthase kinase 3? (GSK3?) modulates antiviral activity of zinc-
RT finger antiviral protein (ZAP).";
RL J. Biol. Chem. 287:22882-22888(2012).
RN [48]
RP CATALYTIC ACTIVITY.
RX PubMed=22539723; DOI=10.1126/science.1217032;
RA Lin S.Y., Li T.Y., Liu Q., Zhang C., Li X., Chen Y., Zhang S.M., Lian G.,
RA Liu Q., Ruan K., Wang Z., Zhang C.S., Chien K.Y., Wu J., Li Q., Han J.,
RA Lin S.C.;
RT "GSK3-TIP60-ULK1 signaling pathway links growth factor deprivation to
RT autophagy.";
RL Science 336:477-481(2012).
RN [49]
RP ADP-RIBOSYLATION BY PARP10.
RX PubMed=23332125; DOI=10.1186/1478-811x-11-5;
RA Feijs K.L., Kleine H., Braczynski A., Forst A.H., Herzog N., Verheugd P.,
RA Linzen U., Kremmer E., Luscher B.;
RT "ARTD10 substrate identification on protein microarrays: regulation of
RT GSK3beta by mono-ADP-ribosylation.";
RL Cell Commun. Signal. 11:5-5(2013).
RN [50]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-390, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [51]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [52]
RP FUNCTION, INTERACTION WITH NCYM, AND PHOSPHORYLATION AT SER-9.
RX PubMed=24391509; DOI=10.1371/journal.pgen.1003996;
RA Suenaga Y., Islam S.M., Alagu J., Kaneko Y., Kato M., Tanaka Y., Kawana H.,
RA Hossain S., Matsumoto D., Yamamoto M., Shoji W., Itami M., Shibata T.,
RA Nakamura Y., Ohira M., Haraguchi S., Takatori A., Nakagawara A.;
RT "NCYM, a Cis-antisense gene of MYCN, encodes a de novo evolved protein that
RT inhibits GSK3beta resulting in the stabilization of MYCN in human
RT neuroblastomas.";
RL PLoS Genet. 10:E1003996-E1003996(2014).
RN [53]
RP PHOSPHORYLATION AT SER-9 AND TYR-216, INTERACTION WITH JPT1, AND
RP SUBCELLULAR LOCATION.
RX PubMed=25169422; DOI=10.1002/jcb.24956;
RA Varisli L., Ozturk B.E., Akyuz G.K., Korkmaz K.S.;
RT "HN1 negatively influences the beta-catenin/E-cadherin interaction, and
RT contributes to migration in prostate cells.";
RL J. Cell. Biochem. 116:170-178(2015).
RN [54]
RP INTERACTION WITH GSKIP, AND COMPLEX FORMATION WITH PRKAR2B AND GSKIP.
RX PubMed=25920809; DOI=10.1016/j.bbamcr.2015.04.013;
RA Loh J.K., Lin C.C., Yang M.C., Chou C.H., Chen W.S., Hong M.C., Cho C.L.,
RA Hsu C.M., Cheng J.T., Chou A.K., Chang C.H., Tseng C.N., Wang C.H.,
RA Lieu A.S., Howng S.L., Hong Y.R.;
RT "GSKIP- and GSK3-mediated anchoring strengthens cAMP/PKA/Drp1 axis
RT signaling in the regulation of mitochondrial elongation.";
RL Biochim. Biophys. Acta 1853:1796-1807(2015).
RN [55]
RP FUNCTION, AND INTERACTION WITH RICTOR.
RX PubMed=25897075; DOI=10.1074/jbc.m114.633057;
RA Koo J., Wu X., Mao Z., Khuri F.R., Sun S.Y.;
RT "Rictor Undergoes Glycogen Synthase Kinase 3 (GSK3)-dependent, FBXW7-
RT mediated Ubiquitination and Proteasomal Degradation.";
RL J. Biol. Chem. 290:14120-14129(2015).
RN [56]
RP INTERACTION WITH GSKIP, AND COMPLEX FORMATION WITH PRKAR2A AND GSKIP.
RX PubMed=27484798; DOI=10.1074/jbc.m116.738047;
RA Dema A., Schroeter M.F., Perets E., Skroblin P., Moutty M.C., Deak V.A.,
RA Birchmeier W., Klussmann E.;
RT "The A-Kinase Anchoring Protein (AKAP) Glycogen Synthase Kinase 3beta
RT Interaction Protein (GSKIP) Regulates beta-Catenin through Its Interactions
RT with Both Protein Kinase A (PKA) and GSK3beta.";
RL J. Biol. Chem. 291:19618-19630(2016).
RN [57]
RP INTERACTION WITH AXIN1 AND GID8.
RX PubMed=28829046; DOI=10.1038/cr.2017.107;
RA Lu Y., Xie S., Zhang W., Zhang C., Gao C., Sun Q., Cai Y., Xu Z., Xiao M.,
RA Xu Y., Huang X., Wu X., Liu W., Wang F., Kang Y., Zhou T.;
RT "Twa1/Gid8 is a beta-catenin nuclear retention factor in Wnt signaling and
RT colorectal tumorigenesis.";
RL Cell Res. 27:1422-1440(2017).
RN [58]
RP FUNCTION, AND INTERACTION WITH ARNTL.
RX PubMed=28903391; DOI=10.18632/oncotarget.18973;
RA Lu Y., Zheng X., Hu W., Bian S., Zhang Z., Tao D., Liu Y., Ma Y.;
RT "Cancer/testis antigen PIWIL2 suppresses circadian rhythms by regulating
RT the stability and activity of BMAL1 and CLOCK.";
RL Oncotarget 8:54913-54924(2017).
RN [59]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF SER-9.
RX PubMed=28992046; DOI=10.1093/jmcb/mjx034;
RA Wang D., Zhao J., Li S., Wei J., Nan L., Mallampalli R.K.,
RA Weathington N.M., Ma H., Zhao Y.;
RT "Phosphorylated E2F1 is stabilized by nuclear USP11 to drive Peg10 gene
RT expression and activate lung epithelial cells.";
RL J. Mol. Cell Biol. 10:60-73(2018).
RN [60]
RP FUNCTION.
RX PubMed=30704899; DOI=10.1016/j.molcel.2018.12.017;
RA Cheng X., Ma X., Zhu Q., Song D., Ding X., Li L., Jiang X., Wang X.,
RA Tian R., Su H., Shen Z., Chen S., Liu T., Gong W., Liu W., Sun Q.;
RT "Pacer is a mediator of mTORC1 and GSK3-TIP60 signaling in regulation of
RT autophagosome maturation and lipid metabolism.";
RL Mol. Cell 73:1-15(2019).
RN [61]
RP INTERACTION WITH LMBR1L.
RX PubMed=31073040; DOI=10.1126/science.aau0812;
RA Choi J.H., Zhong X., McAlpine W., Liao T.C., Zhang D., Fang B., Russell J.,
RA Ludwig S., Nair-Gill E., Zhang Z., Wang K.W., Misawa T., Zhan X., Choi M.,
RA Wang T., Li X., Tang M., Sun Q., Yu L., Murray A.R., Moresco E.M.Y.,
RA Beutler B.;
RT "LMBR1L regulates lymphopoiesis through Wnt/beta-catenin signaling.";
RL Science 364:0-0(2019).
RN [62]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 35-386.
RX PubMed=11440715; DOI=10.1016/s0092-8674(01)00374-9;
RA Dajani R., Fraser E., Roe S.M., Young N., Good V., Dale T.C., Pearl L.H.;
RT "Crystal structure of glycogen synthase kinase 3 beta: structural basis for
RT phosphate-primed substrate specificity and autoinhibition.";
RL Cell 105:721-732(2001).
RN [63]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 27-393 OF PHOSPHORYLATED GSK3B.
RX PubMed=11738041; DOI=10.1016/s0969-2126(01)00679-7;
RA Bax B., Carter P.S., Lewis C., Guy A.R., Bridges A., Tanner R., Pettman G.,
RA Mannix C., Culbert A.A., Brown M.J.B., Smith D.G., Reith A.D.;
RT "The structure of phosphorylated GSK-3beta complexed with a peptide,
RT FRATtide, that inhibits beta-catenin phosphorylation.";
RL Structure 9:1143-1152(2001).
RN [64]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 35-384 IN COMPLEX WITH AXIN1,
RP INTERACTION WITH AXIN1 AND FRAT1, FUNCTION, ACTIVITY REGULATION, AND
RP PHOSPHORYLATION AT TYR-216.
RX PubMed=12554650; DOI=10.1093/emboj/cdg068;
RA Dajani R., Fraser E., Roe S.M., Yeo M., Good V.M., Thompson V., Dale T.C.,
RA Pearl L.H.;
RT "Structural basis for recruitment of glycogen synthase kinase 3beta to the
RT axin-APC scaffold complex.";
RL EMBO J. 22:494-501(2003).
CC -!- FUNCTION: Constitutively active protein kinase that acts as a negative
CC regulator in the hormonal control of glucose homeostasis, Wnt signaling
CC and regulation of transcription factors and microtubules, by
CC phosphorylating and inactivating glycogen synthase (GYS1 or GYS2),
CC EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN,
CC NFATC1/NFATC, MAPT/TAU and MACF1 (PubMed:1846781, PubMed:9072970,
CC PubMed:14690523, PubMed:20937854, PubMed:12554650, PubMed:11430833,
CC PubMed:16484495). Requires primed phosphorylation of the majority of
CC its substrates (PubMed:11430833, PubMed:16484495). In skeletal muscle,
CC contributes to insulin regulation of glycogen synthesis by
CC phosphorylating and inhibiting GYS1 activity and hence glycogen
CC synthesis (PubMed:8397507). May also mediate the development of insulin
CC resistance by regulating activation of transcription factors
CC (PubMed:8397507). Regulates protein synthesis by controlling the
CC activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as
CC glycogen synthase (PubMed:8397507). In Wnt signaling, GSK3B forms a
CC multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and
CC phosphorylates the N-terminus of CTNNB1 leading to its degradation
CC mediated by ubiquitin/proteasomes (PubMed:12554650). Phosphorylates JUN
CC at sites proximal to its DNA-binding domain, thereby reducing its
CC affinity for DNA (PubMed:1846781). Phosphorylates NFATC1/NFATC on
CC conserved serine residues promoting NFATC1/NFATC nuclear export,
CC shutting off NFATC1/NFATC gene regulation, and thereby opposing the
CC action of calcineurin (PubMed:9072970). Phosphorylates MAPT/TAU on
CC 'Thr-548', decreasing significantly MAPT/TAU ability to bind and
CC stabilize microtubules (PubMed:14690523). MAPT/TAU is the principal
CC component of neurofibrillary tangles in Alzheimer disease
CC (PubMed:14690523). Plays an important role in ERBB2-dependent
CC stabilization of microtubules at the cell cortex (PubMed:20937854).
CC Phosphorylates MACF1, inhibiting its binding to microtubules which is
CC critical for its role in bulge stem cell migration and skin wound
CC repair (By similarity). Probably regulates NF-kappa-B (NFKB1) at the
CC transcriptional level and is required for the NF-kappa-B-mediated anti-
CC apoptotic response to TNF-alpha (TNF/TNFA) (By similarity). Negatively
CC regulates replication in pancreatic beta-cells, resulting in apoptosis,
CC loss of beta-cells and diabetes (By similarity). Through
CC phosphorylation of the anti-apoptotic protein MCL1, may control cell
CC apoptosis in response to growth factors deprivation (By similarity).
CC Phosphorylates MUC1 in breast cancer cells, decreasing the interaction
CC of MUC1 with CTNNB1/beta-catenin (PubMed:9819408). Is necessary for the
CC establishment of neuronal polarity and axon outgrowth
CC (PubMed:20067585). Phosphorylates MARK2, leading to inhibition of its
CC activity (By similarity). Phosphorylates SIK1 at 'Thr-182', leading to
CC sustainment of its activity (PubMed:18348280). Phosphorylates ZC3HAV1
CC which enhances its antiviral activity (PubMed:22514281). Phosphorylates
CC SNAI1, leading to its BTRC-triggered ubiquitination and proteasomal
CC degradation (PubMed:15448698, PubMed:15647282). Phosphorylates SFPQ at
CC 'Thr-687' upon T-cell activation (PubMed:20932480). Phosphorylates
CC NR1D1 st 'Ser-55' and 'Ser-59' and stabilizes it by protecting it from
CC proteasomal degradation. Regulates the circadian clock via
CC phosphorylation of the major clock components including ARNTL/BMAL1,
CC CLOCK and PER2 (PubMed:19946213, PubMed:28903391). Phosphorylates CLOCK
CC AT 'Ser-427' and targets it for proteasomal degradation
CC (PubMed:19946213). Phosphorylates ARNTL/BMAL1 at 'Ser-17' and 'Ser-21'
CC and primes it for ubiquitination and proteasomal degradation
CC (PubMed:28903391). Phosphorylates OGT at 'Ser-3' or 'Ser-4' which
CC positively regulates its activity. Phosphorylates MYCN in neuroblastoma
CC cells which may promote its degradation (PubMed:24391509). Regulates
CC the circadian rhythmicity of hippocampal long-term potentiation and
CC ARNTL/BMLA1 and PER2 expression (By similarity). Acts as a regulator of
CC autophagy by mediating phosphorylation of KAT5/TIP60 under starvation
CC conditions, activating KAT5/TIP60 acetyltransferase activity and
CC promoting acetylation of key autophagy regulators, such as ULK1 and
CC RUBCNL/Pacer (PubMed:30704899). Negatively regulates extrinsic
CC apoptotic signaling pathway via death domain receptors. Promotes the
CC formation of an anti-apoptotic complex, made of DDX3X, BRIC2 and GSK3B,
CC at death receptors, including TNFRSF10B. The anti-apoptotic function is
CC most effective with weak apoptotic signals and can be overcome by
CC stronger stimulation (PubMed:18846110). Phosphorylates E2F1, promoting
CC the interaction between E2F1 and USP11, stabilizing E2F1 and promoting
CC its activity (PubMed:17050006, PubMed:28992046). Phosphorylates mTORC2
CC complex component RICTOR at 'Thr-1695' which facilitates FBXW7-mediated
CC ubiquitination and subsequent degradation of RICTOR (PubMed:25897075).
CC {ECO:0000250|UniProtKB:P18266, ECO:0000250|UniProtKB:Q9WV60,
CC ECO:0000269|PubMed:11430833, ECO:0000269|PubMed:12554650,
CC ECO:0000269|PubMed:14690523, ECO:0000269|PubMed:15448698,
CC ECO:0000269|PubMed:15647282, ECO:0000269|PubMed:16484495,
CC ECO:0000269|PubMed:17050006, ECO:0000269|PubMed:18348280,
CC ECO:0000269|PubMed:1846781, ECO:0000269|PubMed:18846110,
CC ECO:0000269|PubMed:19946213, ECO:0000269|PubMed:20067585,
CC ECO:0000269|PubMed:20932480, ECO:0000269|PubMed:20937854,
CC ECO:0000269|PubMed:22514281, ECO:0000269|PubMed:24391509,
CC ECO:0000269|PubMed:25897075, ECO:0000269|PubMed:28903391,
CC ECO:0000269|PubMed:28992046, ECO:0000269|PubMed:30704899,
CC ECO:0000269|PubMed:8397507, ECO:0000269|PubMed:9072970,
CC ECO:0000269|PubMed:9819408}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[tau protein] = ADP + H(+) + O-phospho-L-seryl-
CC [tau protein]; Xref=Rhea:RHEA:12801, Rhea:RHEA-COMP:13701, Rhea:RHEA-
CC COMP:13702, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.26;
CC Evidence={ECO:0000269|PubMed:14690523};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[tau protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[tau protein]; Xref=Rhea:RHEA:53904, Rhea:RHEA-COMP:13703,
CC Rhea:RHEA-COMP:13704, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.26; Evidence={ECO:0000269|PubMed:14690523};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:17050006, ECO:0000269|PubMed:22539723,
CC ECO:0000269|PubMed:28992046};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:17050006};
CC -!- ACTIVITY REGULATION: Activated by phosphorylation at Tyr-216. In
CC response to insulin, inhibited by phosphorylation at Ser-9 by PKB/AKT1
CC and RPS6KA3; phosphorylation at this site causes a conformational
CC change, preventing access of substrates to the active site. Inhibited
CC by lithium. {ECO:0000269|PubMed:11749387, ECO:0000269|PubMed:12554650,
CC ECO:0000269|PubMed:19366350, ECO:0000269|PubMed:8524413}.
CC -!- SUBUNIT: Monomer. Interacts with ARRB2, DISC1 and ZBED3 (By
CC similarity). Interacts with CABYR, MMP2, MUC1, NIN and PRUNE1.
CC Interacts with AXIN1; the interaction mediates hyperphosphorylation of
CC CTNNB1 leading to its ubiquitination and destruction. Interacts with
CC and phosphorylates SNAI1. Interacts with DNM1L (via a C-terminal
CC domain). Found in a complex composed of MACF1, APC, AXIN1, CTNNB1 and
CC GSK3B (By similarity). Interacts with SGK3. Interacts with DAB2IP (via
CC C2 domain); the interaction stimulates GSK3B kinase activation.
CC Interacts (via C2 domain) with PPP2CA. Interacts with the CLOCK-
CC ARNTL/BMAL1 heterodimer (PubMed:19946213). Interacts with the
CC ARNTL/BMAL1 (PubMed:28903391). Interacts with CTNND2 (PubMed:19706605).
CC Interacts with NCYM (PubMed:24391509). The complex composed, at least,
CC of APC, CTNNB1 and GSK3B interacts with JPT1; the interaction requires
CC the inactive form of GSK3B (phosphorylated at 'Ser-9')
CC (PubMed:25169422). Forms a complex composed of PRKAR2A or PRKAR2B,
CC GSK3B and GSKIP through GSKIP interaction; facilitates PKA-induced
CC phosphorylation and regulates GSK3B activity (PubMed:27484798,
CC PubMed:20007971, PubMed:25920809). Interacts with GSKIP
CC (PubMed:16981698). Interacts with GID8 (PubMed:28829046). Interacts
CC with PIWIL2 (By similarity). Interacts with LMBR1L (PubMed:31073040).
CC Interacts with DDX3X (PubMed:18846110). Interacts with BIRC2
CC (PubMed:18846110). Interacts with TNFRSF10B; TNFRSF10B stimulation
CC inhibits GSK3B kinase activity (PubMed:18846110). Interacts with
CC RICTOR; the interaction results in phosphorylation of RICTOR at 'Thr-
CC 1695' by GSK3B which facilitates FBXW7-mediated ubiquitination and
CC subsequent degradation of RICTOR (PubMed:25897075).
CC {ECO:0000250|UniProtKB:P18266, ECO:0000250|UniProtKB:Q9WV60,
CC ECO:0000269|PubMed:11004522, ECO:0000269|PubMed:12054501,
CC ECO:0000269|PubMed:12554650, ECO:0000269|PubMed:15448698,
CC ECO:0000269|PubMed:15647282, ECO:0000269|PubMed:15752768,
CC ECO:0000269|PubMed:16428445, ECO:0000269|PubMed:16981698,
CC ECO:0000269|PubMed:17318175, ECO:0000269|PubMed:18846110,
CC ECO:0000269|PubMed:19493954, ECO:0000269|PubMed:19706605,
CC ECO:0000269|PubMed:19946213, ECO:0000269|PubMed:20007971,
CC ECO:0000269|PubMed:20080667, ECO:0000269|PubMed:24391509,
CC ECO:0000269|PubMed:25169422, ECO:0000269|PubMed:25897075,
CC ECO:0000269|PubMed:25920809, ECO:0000269|PubMed:27484798,
CC ECO:0000269|PubMed:28829046, ECO:0000269|PubMed:28903391,
CC ECO:0000269|PubMed:31073040, ECO:0000269|PubMed:9731200,
CC ECO:0000269|PubMed:9819408}.
CC -!- INTERACTION:
CC P49841; P31749: AKT1; NbExp=4; IntAct=EBI-373586, EBI-296087;
CC P49841; P31751: AKT2; NbExp=2; IntAct=EBI-373586, EBI-296058;
CC P49841; PRO_0000000093 [P05067]: APP; NbExp=2; IntAct=EBI-373586, EBI-2431589;
CC P49841; O15169: AXIN1; NbExp=51; IntAct=EBI-373586, EBI-710484;
CC P49841; Q96G01: BICD1; NbExp=7; IntAct=EBI-373586, EBI-1104509;
CC P49841; O75952-3: CABYR; NbExp=3; IntAct=EBI-373586, EBI-10900795;
CC P49841; O75952-5: CABYR; NbExp=3; IntAct=EBI-373586, EBI-10898671;
CC P49841; P35222: CTNNB1; NbExp=19; IntAct=EBI-373586, EBI-491549;
CC P49841; Q5VWQ8: DAB2IP; NbExp=2; IntAct=EBI-373586, EBI-2871881;
CC P49841; Q5VWQ8-2: DAB2IP; NbExp=2; IntAct=EBI-373586, EBI-9543020;
CC P49841; Q9NYF0: DACT1; NbExp=3; IntAct=EBI-373586, EBI-3951744;
CC P49841; O75398: DEAF1; NbExp=2; IntAct=EBI-373586, EBI-718185;
CC P49841; Q13144: EIF2B5; NbExp=2; IntAct=EBI-373586, EBI-4401110;
CC P49841; Q92837: FRAT1; NbExp=5; IntAct=EBI-373586, EBI-3934879;
CC P49841; P13807: GYS1; NbExp=4; IntAct=EBI-373586, EBI-740553;
CC P49841; O75581: LRP6; NbExp=4; IntAct=EBI-373586, EBI-910915;
CC P49841; Q5S007: LRRK2; NbExp=7; IntAct=EBI-373586, EBI-5323863;
CC P49841; P10636: MAPT; NbExp=4; IntAct=EBI-373586, EBI-366182;
CC P49841; P10636-8: MAPT; NbExp=9; IntAct=EBI-373586, EBI-366233;
CC P49841; Q14596: NBR1; NbExp=4; IntAct=EBI-373586, EBI-742698;
CC P49841; Q8N4C6: NIN; NbExp=3; IntAct=EBI-373586, EBI-1164022;
CC P49841; P17612: PRKACA; NbExp=7; IntAct=EBI-373586, EBI-476586;
CC P49841; Q01201: RELB; NbExp=4; IntAct=EBI-373586, EBI-357837;
CC P49841; O95863: SNAI1; NbExp=5; IntAct=EBI-373586, EBI-1045459;
CC P49841; P37840: SNCA; NbExp=2; IntAct=EBI-373586, EBI-985879;
CC P49841; Q6J9G0: STYK1; NbExp=2; IntAct=EBI-373586, EBI-6424915;
CC P49841; P04637: TP53; NbExp=3; IntAct=EBI-373586, EBI-366083;
CC P49841; Q14134: TRIM29; NbExp=2; IntAct=EBI-373586, EBI-702370;
CC P49841; O95071: UBR5; NbExp=8; IntAct=EBI-373586, EBI-358329;
CC P49841; P63104: YWHAZ; NbExp=4; IntAct=EBI-373586, EBI-347088;
CC P49841; Q8IX07: ZFPM1; NbExp=2; IntAct=EBI-373586, EBI-3942619;
CC P49841; O35625: Axin1; Xeno; NbExp=5; IntAct=EBI-373586, EBI-2365912;
CC P49841; Q14DJ8: Axin1; Xeno; NbExp=2; IntAct=EBI-373586, EBI-4312125;
CC P49841; Q02248: Ctnnb1; Xeno; NbExp=3; IntAct=EBI-373586, EBI-397872;
CC P49841; Q811T9: Disc1; Xeno; NbExp=4; IntAct=EBI-373586, EBI-2298259;
CC P49841; P63085: Mapk1; Xeno; NbExp=2; IntAct=EBI-373586, EBI-397697;
CC P49841; P0DTC9: N; Xeno; NbExp=3; IntAct=EBI-373586, EBI-25475856;
CC P49841-2; P05067: APP; NbExp=3; IntAct=EBI-15870655, EBI-77613;
CC P49841-2; P35637: FUS; NbExp=3; IntAct=EBI-15870655, EBI-400434;
CC P49841-2; P01106: MYC; NbExp=3; IntAct=EBI-15870655, EBI-447544;
CC P49841-2; Q8BMD2-1: Dzip1; Xeno; NbExp=3; IntAct=EBI-15870655, EBI-16153101;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21029237,
CC ECO:0000269|PubMed:25169422}. Nucleus {ECO:0000269|PubMed:15448698,
CC ECO:0000269|PubMed:21029237}. Cell membrane
CC {ECO:0000269|PubMed:20937854}. Note=The phosphorylated form shows
CC localization to cytoplasm and cell membrane (PubMed:20937854). The
CC MEMO1-RHOA-DIAPH1 signaling pathway controls localization of the
CC phosphorylated form to the cell membrane (PubMed:20937854).
CC {ECO:0000269|PubMed:20937854}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=GSK-3beta1;
CC IsoId=P49841-1; Sequence=Displayed;
CC Name=2; Synonyms=GSK-3beta2, neuron-specific;
CC IsoId=P49841-2; Sequence=VSP_004790;
CC -!- TISSUE SPECIFICITY: Expressed in testis, thymus, prostate and ovary and
CC weakly expressed in lung, brain and kidney. Colocalizes with
CC EIF2AK2/PKR and TAU in the Alzheimer disease (AD) brain.
CC {ECO:0000269|PubMed:21029237}.
CC -!- PTM: Phosphorylated by AKT1 and ILK1. Upon insulin-mediated signaling,
CC the activated PKB/AKT1 protein kinase phosphorylates and deactivates
CC GSK3B, resulting in the dephosphorylation and activation of GYS1.
CC Activated by phosphorylation at Tyr-216 (PubMed:25169422). Inactivated
CC by phosphorylation at Ser-9 (Probable). Phosphorylated in a circadian
CC manner in the hippocampus (By similarity).
CC {ECO:0000250|UniProtKB:Q9WV60, ECO:0000269|PubMed:12054501,
CC ECO:0000269|PubMed:12554650, ECO:0000269|PubMed:16484495,
CC ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:21029237,
CC ECO:0000269|PubMed:25169422, ECO:0000269|PubMed:8250835,
CC ECO:0000305|PubMed:25169422}.
CC -!- PTM: Mono-ADP-ribosylation by PARP10 negatively regulates kinase
CC activity. {ECO:0000269|PubMed:23332125}.
CC -!- MISCELLANEOUS: Higher expression and activity of GSK3B are found in the
CC skeletal muscle (vastus lateralis) of patients with type 2 diabetes
CC (PubMed:10868943). Several potent GSK3 (GSK3A and GSK3B) inhibitors
CC have been identified and characterized in preclinical models for
CC treatments of type 2 diabetes (PubMed:19366350).
CC {ECO:0000305|PubMed:10868943, ECO:0000305|PubMed:19366350}.
CC -!- MISCELLANEOUS: [Isoform 2]: May play a specific role in axon growth and
CC neurite outgrowth. Reduced binding to AXIN1, reduced ability to
CC phosphorylate MAPT/TAU. {ECO:0000269|PubMed:20067585}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. GSK-3 subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/GSK3BID40761ch3q13.html";
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DR EMBL; L33801; AAA66475.1; -; mRNA.
DR EMBL; CH471052; EAW79533.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79536.1; -; Genomic_DNA.
DR EMBL; BC000251; AAH00251.1; -; mRNA.
DR EMBL; BC012760; AAH12760.1; -; mRNA.
DR EMBL; AF074333; AAD48517.1; -; Genomic_DNA.
DR EMBL; AF098789; AAC69340.1; -; Genomic_DNA.
DR CCDS; CCDS2996.1; -. [P49841-2]
DR CCDS; CCDS54628.1; -. [P49841-1]
DR PIR; S53324; S53324.
DR RefSeq; NP_001139628.1; NM_001146156.1. [P49841-1]
DR RefSeq; NP_002084.2; NM_002093.3. [P49841-2]
DR PDB; 1GNG; X-ray; 2.60 A; A/B=27-393.
DR PDB; 1H8F; X-ray; 2.80 A; A/B=35-386.
DR PDB; 1I09; X-ray; 2.70 A; A/B=1-420.
DR PDB; 1J1B; X-ray; 1.80 A; A/B=1-420.
DR PDB; 1J1C; X-ray; 2.10 A; A/B=1-420.
DR PDB; 1O6K; X-ray; 1.70 A; C=3-12.
DR PDB; 1O6L; X-ray; 1.60 A; C=3-12.
DR PDB; 1O9U; X-ray; 2.40 A; A=35-384.
DR PDB; 1PYX; X-ray; 2.40 A; A/B=1-420.
DR PDB; 1Q3D; X-ray; 2.20 A; A/B=2-420.
DR PDB; 1Q3W; X-ray; 2.30 A; A/B=2-420.
DR PDB; 1Q41; X-ray; 2.10 A; A/B=2-420.
DR PDB; 1Q4L; X-ray; 2.77 A; A/B=2-420.
DR PDB; 1Q5K; X-ray; 1.94 A; A/B=7-420.
DR PDB; 1R0E; X-ray; 2.25 A; A/B=35-420.
DR PDB; 1UV5; X-ray; 2.80 A; A=35-384.
DR PDB; 2JDO; X-ray; 1.80 A; C=3-12.
DR PDB; 2JDR; X-ray; 2.30 A; C=3-12.
DR PDB; 2JLD; X-ray; 2.35 A; A/B=1-420.
DR PDB; 2O5K; X-ray; 3.20 A; A=29-393.
DR PDB; 2OW3; X-ray; 2.80 A; A/B=35-386.
DR PDB; 2UW9; X-ray; 2.10 A; C=3-12.
DR PDB; 2X39; X-ray; 1.93 A; C=3-12.
DR PDB; 2XH5; X-ray; 2.72 A; C=3-12.
DR PDB; 3CQU; X-ray; 2.20 A; C=3-12.
DR PDB; 3CQW; X-ray; 2.00 A; C=3-12.
DR PDB; 3DU8; X-ray; 2.20 A; A/B=1-420.
DR PDB; 3E87; X-ray; 2.30 A; C/D=3-12.
DR PDB; 3E88; X-ray; 2.50 A; C/D=3-12.
DR PDB; 3E8D; X-ray; 2.70 A; C/D=3-12.
DR PDB; 3F7Z; X-ray; 2.40 A; A/B=35-383.
DR PDB; 3F88; X-ray; 2.60 A; A/B=35-383.
DR PDB; 3GB2; X-ray; 2.40 A; A=34-383.
DR PDB; 3I4B; X-ray; 2.30 A; A/B=7-420.
DR PDB; 3L1S; X-ray; 2.90 A; A/B=7-420.
DR PDB; 3M1S; X-ray; 3.13 A; A/B=1-420.
DR PDB; 3MV5; X-ray; 2.47 A; C=3-12.
DR PDB; 3OW4; X-ray; 2.60 A; C/D=3-12.
DR PDB; 3PUP; X-ray; 2.99 A; A/B=1-420.
DR PDB; 3Q3B; X-ray; 2.70 A; A/B=2-420.
DR PDB; 3QKK; X-ray; 2.30 A; C=3-12.
DR PDB; 3SAY; X-ray; 2.23 A; A/B=1-420.
DR PDB; 3SD0; X-ray; 2.70 A; A/B=35-384.
DR PDB; 3ZDI; X-ray; 2.64 A; A=35-384.
DR PDB; 3ZRK; X-ray; 2.37 A; A/B=23-393.
DR PDB; 3ZRL; X-ray; 2.48 A; A/B=23-393.
DR PDB; 3ZRM; X-ray; 2.49 A; A/B=23-393.
DR PDB; 4ACC; X-ray; 2.21 A; A/B=1-420.
DR PDB; 4ACD; X-ray; 2.60 A; A/B=1-420.
DR PDB; 4ACG; X-ray; 2.60 A; A/B=1-420.
DR PDB; 4ACH; X-ray; 2.60 A; A/B=1-420.
DR PDB; 4AFJ; X-ray; 1.98 A; A/B=27-393.
DR PDB; 4B7T; X-ray; 2.77 A; A=35-384.
DR PDB; 4DIT; X-ray; 2.60 A; A=27-393.
DR PDB; 4EKK; X-ray; 2.80 A; C/D=3-12.
DR PDB; 4IQ6; X-ray; 3.12 A; A/B=1-420.
DR PDB; 4J1R; X-ray; 2.70 A; A/B/C/D=1-420.
DR PDB; 4J71; X-ray; 2.31 A; A/B=1-420.
DR PDB; 4NM0; X-ray; 2.50 A; A=1-383.
DR PDB; 4NM3; X-ray; 2.10 A; A=1-383.
DR PDB; 4NM5; X-ray; 2.30 A; A=13-383.
DR PDB; 4NM7; X-ray; 2.30 A; A=13-383.
DR PDB; 4PTC; X-ray; 2.71 A; A/B=1-420.
DR PDB; 4PTE; X-ray; 2.03 A; A/B=1-420.
DR PDB; 4PTG; X-ray; 2.36 A; A/B=1-420.
DR PDB; 5F94; X-ray; 2.51 A; A/B=36-385.
DR PDB; 5F95; X-ray; 2.52 A; A/B=36-385.
DR PDB; 5HLN; X-ray; 3.10 A; A/B=1-420.
DR PDB; 5HLP; X-ray; 2.45 A; A/B=1-420.
DR PDB; 5K5N; X-ray; 2.20 A; A/B=28-384.
DR PDB; 5KPK; X-ray; 2.40 A; A/B=1-420.
DR PDB; 5KPL; X-ray; 2.60 A; A/B=1-420.
DR PDB; 5KPM; X-ray; 2.69 A; A/B=1-420.
DR PDB; 5OY4; X-ray; 3.20 A; A/B=1-420.
DR PDB; 5T31; X-ray; 2.85 A; A/B=1-420.
DR PDB; 6B8J; X-ray; 2.60 A; A=1-420.
DR PDB; 6BUU; X-ray; 2.40 A; F/G=3-12.
DR PDB; 6GJO; X-ray; 2.91 A; A/B=7-420.
DR PDB; 6GN1; X-ray; 2.60 A; A/B=27-393.
DR PDB; 6H0U; X-ray; 2.30 A; A/B=1-420.
DR PDB; 6HK3; X-ray; 2.35 A; A/B=35-384.
DR PDB; 6HK4; X-ray; 2.50 A; A/B=35-384.
DR PDB; 6HK7; X-ray; 3.20 A; A=36-382.
DR PDB; 6NPZ; X-ray; 2.12 A; F/G=3-12.
DR PDB; 6TCU; X-ray; 2.14 A; A=35-386.
DR PDB; 6V6L; X-ray; 2.19 A; A=1-420.
DR PDB; 6Y9R; X-ray; 2.08 A; A=35-384.
DR PDB; 6Y9S; X-ray; 2.03 A; A/B=35-384.
DR PDB; 7B6F; X-ray; 2.05 A; A=26-383.
DR PDB; 7OY5; X-ray; 2.57 A; A/B=35-385.
DR PDBsum; 1GNG; -.
DR PDBsum; 1H8F; -.
DR PDBsum; 1I09; -.
DR PDBsum; 1J1B; -.
DR PDBsum; 1J1C; -.
DR PDBsum; 1O6K; -.
DR PDBsum; 1O6L; -.
DR PDBsum; 1O9U; -.
DR PDBsum; 1PYX; -.
DR PDBsum; 1Q3D; -.
DR PDBsum; 1Q3W; -.
DR PDBsum; 1Q41; -.
DR PDBsum; 1Q4L; -.
DR PDBsum; 1Q5K; -.
DR PDBsum; 1R0E; -.
DR PDBsum; 1UV5; -.
DR PDBsum; 2JDO; -.
DR PDBsum; 2JDR; -.
DR PDBsum; 2JLD; -.
DR PDBsum; 2O5K; -.
DR PDBsum; 2OW3; -.
DR PDBsum; 2UW9; -.
DR PDBsum; 2X39; -.
DR PDBsum; 2XH5; -.
DR PDBsum; 3CQU; -.
DR PDBsum; 3CQW; -.
DR PDBsum; 3DU8; -.
DR PDBsum; 3E87; -.
DR PDBsum; 3E88; -.
DR PDBsum; 3E8D; -.
DR PDBsum; 3F7Z; -.
DR PDBsum; 3F88; -.
DR PDBsum; 3GB2; -.
DR PDBsum; 3I4B; -.
DR PDBsum; 3L1S; -.
DR PDBsum; 3M1S; -.
DR PDBsum; 3MV5; -.
DR PDBsum; 3OW4; -.
DR PDBsum; 3PUP; -.
DR PDBsum; 3Q3B; -.
DR PDBsum; 3QKK; -.
DR PDBsum; 3SAY; -.
DR PDBsum; 3SD0; -.
DR PDBsum; 3ZDI; -.
DR PDBsum; 3ZRK; -.
DR PDBsum; 3ZRL; -.
DR PDBsum; 3ZRM; -.
DR PDBsum; 4ACC; -.
DR PDBsum; 4ACD; -.
DR PDBsum; 4ACG; -.
DR PDBsum; 4ACH; -.
DR PDBsum; 4AFJ; -.
DR PDBsum; 4B7T; -.
DR PDBsum; 4DIT; -.
DR PDBsum; 4EKK; -.
DR PDBsum; 4IQ6; -.
DR PDBsum; 4J1R; -.
DR PDBsum; 4J71; -.
DR PDBsum; 4NM0; -.
DR PDBsum; 4NM3; -.
DR PDBsum; 4NM5; -.
DR PDBsum; 4NM7; -.
DR PDBsum; 4PTC; -.
DR PDBsum; 4PTE; -.
DR PDBsum; 4PTG; -.
DR PDBsum; 5F94; -.
DR PDBsum; 5F95; -.
DR PDBsum; 5HLN; -.
DR PDBsum; 5HLP; -.
DR PDBsum; 5K5N; -.
DR PDBsum; 5KPK; -.
DR PDBsum; 5KPL; -.
DR PDBsum; 5KPM; -.
DR PDBsum; 5OY4; -.
DR PDBsum; 5T31; -.
DR PDBsum; 6B8J; -.
DR PDBsum; 6BUU; -.
DR PDBsum; 6GJO; -.
DR PDBsum; 6GN1; -.
DR PDBsum; 6H0U; -.
DR PDBsum; 6HK3; -.
DR PDBsum; 6HK4; -.
DR PDBsum; 6HK7; -.
DR PDBsum; 6NPZ; -.
DR PDBsum; 6TCU; -.
DR PDBsum; 6V6L; -.
DR PDBsum; 6Y9R; -.
DR PDBsum; 6Y9S; -.
DR PDBsum; 7B6F; -.
DR PDBsum; 7OY5; -.
DR AlphaFoldDB; P49841; -.
DR SMR; P49841; -.
DR BioGRID; 109187; 640.
DR ComplexPortal; CPX-109; Beta-catenin destruction core complex, variant 1.
DR ComplexPortal; CPX-439; Beta-catenin destruction core complex, variant 3.
DR ComplexPortal; CPX-440; Beta-catenin destruction core complex, variant 4.
DR ComplexPortal; CPX-459; Nuclear export complex FRAT1-GSK3B.
DR ComplexPortal; CPX-462; Nuclear export complex FRAT2-GSK3B.
DR ComplexPortal; CPX-99; Beta-catenin destruction core complex, variant 2.
DR CORUM; P49841; -.
DR DIP; DIP-878N; -.
DR ELM; P49841; -.
DR IntAct; P49841; 346.
DR MINT; P49841; -.
DR STRING; 9606.ENSP00000324806; -.
DR BindingDB; P49841; -.
DR ChEMBL; CHEMBL262; -.
DR DrugBank; DB08073; (2S)-1-(1H-INDOL-3-YL)-3-{[5-(3-METHYL-1H-INDAZOL-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINE.
DR DrugBank; DB07149; (7S)-2-(2-aminopyrimidin-4-yl)-7-(2-fluoroethyl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one.
DR DrugBank; DB07014; 2-(1,3-benzodioxol-5-yl)-5-[(3-fluoro-4-methoxybenzyl)sulfanyl]-1,3,4-oxadiazole.
DR DrugBank; DB07676; 3-({[(3S)-3,4-dihydroxybutyl]oxy}amino)-1H,2'H-2,3'-biindol-2'-one.
DR DrugBank; DB01772; 3-[3-(2,3-Dihydroxy-Propylamino)-Phenyl]-4-(5-Fluoro-1-Methyl-1h-Indol-3-Yl)-Pyrrole-2,5-Dione.
DR DrugBank; DB07859; 4-(4-CHLOROPHENYL)-4-[4-(1H-PYRAZOL-4-YL)PHENYL]PIPERIDINE.
DR DrugBank; DB07585; 5-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine.
DR DrugBank; DB07058; 5-[1-(4-methoxyphenyl)-1H-benzimidazol-6-yl]-1,3,4-oxadiazole-2(3H)-thione.
DR DrugBank; DB03444; 6-bromoindirubin-3'-oxime.
DR DrugBank; DB04014; Alsterpaullone.
DR DrugBank; DB01950; AR-AO-14418.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB02052; Indirubin-3'-monoxime.
DR DrugBank; DB07947; ISOQUINOLINE-5-SULFONIC ACID (2-(2-(4-CHLOROBENZYLOXY)ETHYLAMINO)ETHYL)AMIDE.
DR DrugBank; DB14509; Lithium carbonate.
DR DrugBank; DB01356; Lithium cation.
DR DrugBank; DB14507; Lithium citrate.
DR DrugBank; DB14508; Lithium succinate.
DR DrugBank; DB07812; N-[(1S)-2-amino-1-phenylethyl]-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)thiophene-2-carboxamide.
DR DrugBank; DB07584; N-[2-(5-methyl-4H-1,2,4-triazol-3-yl)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine.
DR DrugBank; DB04395; Phosphoaminophosphonic Acid-Adenylate Ester.
DR DrugBank; DB01793; SB-409513.
DR DrugBank; DB02010; Staurosporine.
DR DrugBank; DB12129; Tideglusib.
DR DrugCentral; P49841; -.
DR GuidetoPHARMACOLOGY; 2030; -.
DR GlyGen; P49841; 3 sites, 1 O-linked glycan (3 sites).
DR iPTMnet; P49841; -.
DR PhosphoSitePlus; P49841; -.
DR BioMuta; GSK3B; -.
DR DMDM; 20455502; -.
DR CPTAC; CPTAC-804; -.
DR EPD; P49841; -.
DR jPOST; P49841; -.
DR MassIVE; P49841; -.
DR MaxQB; P49841; -.
DR PaxDb; P49841; -.
DR PeptideAtlas; P49841; -.
DR PRIDE; P49841; -.
DR ProteomicsDB; 56151; -. [P49841-1]
DR ProteomicsDB; 56152; -. [P49841-2]
DR Antibodypedia; 4266; 1408 antibodies from 53 providers.
DR CPTC; P49841; 10 antibodies.
DR DNASU; 2932; -.
DR Ensembl; ENST00000264235.13; ENSP00000264235.9; ENSG00000082701.17. [P49841-1]
DR Ensembl; ENST00000316626.6; ENSP00000324806.5; ENSG00000082701.17. [P49841-2]
DR GeneID; 2932; -.
DR KEGG; hsa:2932; -.
DR MANE-Select; ENST00000264235.13; ENSP00000264235.9; NM_001146156.2; NP_001139628.1.
DR UCSC; uc003edn.4; human. [P49841-1]
DR CTD; 2932; -.
DR DisGeNET; 2932; -.
DR GeneCards; GSK3B; -.
DR HGNC; HGNC:4617; GSK3B.
DR HPA; ENSG00000082701; Low tissue specificity.
DR MIM; 605004; gene.
DR neXtProt; NX_P49841; -.
DR OpenTargets; ENSG00000082701; -.
DR PharmGKB; PA29009; -.
DR VEuPathDB; HostDB:ENSG00000082701; -.
DR eggNOG; KOG0658; Eukaryota.
DR GeneTree; ENSGT00520000055635; -.
DR HOGENOM; CLU_000288_181_20_1; -.
DR InParanoid; P49841; -.
DR OMA; EMQYTQC; -.
DR OrthoDB; 990896at2759; -.
DR PhylomeDB; P49841; -.
DR TreeFam; TF101104; -.
DR BRENDA; 2.7.11.26; 2681.
DR PathwayCommons; P49841; -.
DR Reactome; R-HSA-195253; Degradation of beta-catenin by the destruction complex.
DR Reactome; R-HSA-196299; Beta-catenin phosphorylation cascade.
DR Reactome; R-HSA-198323; AKT phosphorylates targets in the cytosol.
DR Reactome; R-HSA-3371453; Regulation of HSF1-mediated heat shock response.
DR Reactome; R-HSA-399956; CRMPs in Sema3A signaling.
DR Reactome; R-HSA-4641262; Disassembly of the destruction complex and recruitment of AXIN to the membrane.
DR Reactome; R-HSA-5250924; B-WICH complex positively regulates rRNA expression.
DR Reactome; R-HSA-5339716; Signaling by GSK3beta mutants.
DR Reactome; R-HSA-5358747; CTNNB1 S33 mutants aren't phosphorylated.
DR Reactome; R-HSA-5358749; CTNNB1 S37 mutants aren't phosphorylated.
DR Reactome; R-HSA-5358751; CTNNB1 S45 mutants aren't phosphorylated.
DR Reactome; R-HSA-5358752; CTNNB1 T41 mutants aren't phosphorylated.
DR Reactome; R-HSA-5467337; APC truncation mutants have impaired AXIN binding.
DR Reactome; R-HSA-5467340; AXIN missense mutants destabilize the destruction complex.
DR Reactome; R-HSA-5467348; Truncations of AMER1 destabilize the destruction complex.
DR Reactome; R-HSA-5610783; Degradation of GLI2 by the proteasome.
DR Reactome; R-HSA-5610785; GLI3 is processed to GLI3R by the proteasome.
DR Reactome; R-HSA-5674400; Constitutive Signaling by AKT1 E17K in Cancer.
DR Reactome; R-HSA-75815; Ubiquitin-dependent degradation of Cyclin D.
DR Reactome; R-HSA-8939902; Regulation of RUNX2 expression and activity.
DR Reactome; R-HSA-9683610; Maturation of nucleoprotein.
DR Reactome; R-HSA-9694631; Maturation of nucleoprotein.
DR Reactome; R-HSA-9762114; GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2.
DR SignaLink; P49841; -.
DR SIGNOR; P49841; -.
DR BioGRID-ORCS; 2932; 68 hits in 1132 CRISPR screens.
DR ChiTaRS; GSK3B; human.
DR EvolutionaryTrace; P49841; -.
DR GeneWiki; GSK3B; -.
DR GenomeRNAi; 2932; -.
DR Pharos; P49841; Tclin.
DR PRO; PR:P49841; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P49841; protein.
DR Bgee; ENSG00000082701; Expressed in calcaneal tendon and 195 other tissues.
DR ExpressionAtlas; P49841; baseline and differential.
DR Genevisible; P49841; HS.
DR GO; GO:0030424; C:axon; ISS:ARUK-UCL.
DR GO; GO:0030877; C:beta-catenin destruction complex; IDA:UniProtKB.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0030425; C:dendrite; ISS:ARUK-UCL.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005739; C:mitochondrion; IEA:GOC.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0098794; C:postsynapse; IEA:GOC.
DR GO; GO:1990909; C:Wnt signalosome; TAS:ParkinsonsUK-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008013; F:beta-catenin binding; IPI:BHF-UCL.
DR GO; GO:0034452; F:dynactin binding; IPI:ARUK-UCL.
DR GO; GO:0016301; F:kinase activity; IDA:UniProtKB.
DR GO; GO:0051059; F:NF-kappaB binding; IPI:UniProtKB.
DR GO; GO:0002039; F:p53 binding; IDA:MGI.
DR GO; GO:0002020; F:protease binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0034236; F:protein kinase A catalytic subunit binding; IPI:BHF-UCL.
DR GO; GO:0004672; F:protein kinase activity; IMP:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IGI:ARUK-UCL.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0048156; F:tau protein binding; NAS:ARUK-UCL.
DR GO; GO:0050321; F:tau-protein kinase activity; IDA:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:BHF-UCL.
DR GO; GO:1904886; P:beta-catenin destruction complex disassembly; IDA:ComplexPortal.
DR GO; GO:1904646; P:cellular response to amyloid-beta; ISS:ARUK-UCL.
DR GO; GO:0036016; P:cellular response to interleukin-3; ISS:UniProtKB.
DR GO; GO:0071300; P:cellular response to retinoic acid; IMP:ARUK-UCL.
DR GO; GO:0007623; P:circadian rhythm; ISS:UniProtKB.
DR GO; GO:0007212; P:dopamine receptor signaling pathway; NAS:ParkinsonsUK-UCL.
DR GO; GO:0001837; P:epithelial to mesenchymal transition; IMP:UniProtKB.
DR GO; GO:0006983; P:ER overload response; IDA:MGI.
DR GO; GO:0030010; P:establishment of cell polarity; ISS:ARUK-UCL.
DR GO; GO:0060079; P:excitatory postsynaptic potential; NAS:ParkinsonsUK-UCL.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; ISS:ARUK-UCL.
DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; ISS:UniProtKB.
DR GO; GO:0005977; P:glycogen metabolic process; IDA:BHF-UCL.
DR GO; GO:0021766; P:hippocampus development; IMP:BHF-UCL.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:MGI.
DR GO; GO:0030011; P:maintenance of cell polarity; ISS:ARUK-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:MGI.
DR GO; GO:0070885; P:negative regulation of calcineurin-NFAT signaling cascade; IMP:UniProtKB.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IGI:ARUK-UCL.
DR GO; GO:1905240; P:negative regulation of canonical Wnt signaling pathway involved in osteoblast differentiation; IMP:ARUK-UCL.
DR GO; GO:1904339; P:negative regulation of dopaminergic neuron differentiation; TAS:ParkinsonsUK-UCL.
DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; IMP:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:ARUK-UCL.
DR GO; GO:2000466; P:negative regulation of glycogen (starch) synthase activity; TAS:UniProtKB.
DR GO; GO:0045719; P:negative regulation of glycogen biosynthetic process; TAS:UniProtKB.
DR GO; GO:2000740; P:negative regulation of mesenchymal stem cell differentiation; IMP:ARUK-UCL.
DR GO; GO:1901215; P:negative regulation of neuron death; IDA:UniProtKB.
DR GO; GO:0032515; P:negative regulation of phosphoprotein phosphatase activity; TAS:ARUK-UCL.
DR GO; GO:1901984; P:negative regulation of protein acetylation; ISS:ARUK-UCL.
DR GO; GO:0032091; P:negative regulation of protein binding; IDA:BHF-UCL.
DR GO; GO:1900181; P:negative regulation of protein localization to nucleus; ISS:BHF-UCL.
DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; IMP:BHF-UCL.
DR GO; GO:2000077; P:negative regulation of type B pancreatic cell development; TAS:UniProtKB.
DR GO; GO:0031175; P:neuron projection development; IDA:UniProtKB.
DR GO; GO:0106027; P:neuron projection organization; ISS:ARUK-UCL.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:ParkinsonsUK-UCL.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:ParkinsonsUK-UCL.
DR GO; GO:0010508; P:positive regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0045597; P:positive regulation of cell differentiation; IMP:ARUK-UCL.
DR GO; GO:0001954; P:positive regulation of cell-matrix adhesion; IMP:BHF-UCL.
DR GO; GO:0045724; P:positive regulation of cilium assembly; ISS:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:ARUK-UCL.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IMP:BHF-UCL.
DR GO; GO:1901030; P:positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:0010822; P:positive regulation of mitochondrion organization; IMP:ParkinsonsUK-UCL.
DR GO; GO:1901216; P:positive regulation of neuron death; IDA:ParkinsonsUK-UCL.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:FlyBase.
DR GO; GO:0032092; P:positive regulation of protein binding; ISS:UniProtKB.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IC:BHF-UCL.
DR GO; GO:0046827; P:positive regulation of protein export from nucleus; IDA:MGI.
DR GO; GO:1904781; P:positive regulation of protein localization to centrosome; IMP:ARUK-UCL.
DR GO; GO:1903566; P:positive regulation of protein localization to cilium; ISS:UniProtKB.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; IDA:BHF-UCL.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IC:ComplexPortal.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0030516; P:regulation of axon extension; ISS:ARUK-UCL.
DR GO; GO:0050770; P:regulation of axonogenesis; ISS:ARUK-UCL.
DR GO; GO:1900034; P:regulation of cellular response to heat; TAS:Reactome.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0048814; P:regulation of dendrite morphogenesis; ISS:ARUK-UCL.
DR GO; GO:1900271; P:regulation of long-term synaptic potentiation; ISS:UniProtKB.
DR GO; GO:0150101; P:regulation of microtubule anchoring at centrosome; IMP:ARUK-UCL.
DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; ISS:ARUK-UCL.
DR GO; GO:0032886; P:regulation of microtubule-based process; IMP:UniProtKB.
DR GO; GO:0010975; P:regulation of neuron projection development; IBA:GO_Central.
DR GO; GO:0046825; P:regulation of protein export from nucleus; IDA:ComplexPortal.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IDA:SynGO.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0071109; P:superior temporal gyrus development; IMP:BHF-UCL.
DR GO; GO:0019082; P:viral protein processing; TAS:Reactome.
DR CDD; cd14137; STKc_GSK3; 1.
DR DisProt; DP00385; -.
DR IDEAL; IID00052; -.
DR InterPro; IPR033573; GSK3B.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR039192; STKc_GSK3.
DR PANTHER; PTHR24057:SF8; PTHR24057:SF8; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ADP-ribosylation; Alternative splicing; Alzheimer disease;
KW ATP-binding; Biological rhythms; Carbohydrate metabolism; Cell membrane;
KW Cytoplasm; Developmental protein; Diabetes mellitus; Differentiation;
KW Glycogen metabolism; Kinase; Membrane; Neurogenesis; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Signal transduction inhibitor;
KW Transferase; Wnt signaling pathway.
FT CHAIN 1..420
FT /note="Glycogen synthase kinase-3 beta"
FT /id="PRO_0000085980"
FT DOMAIN 56..340
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..53
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 386..420
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..25
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 181
FT /note="Proton acceptor"
FT BINDING 62..70
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 85
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000305|PubMed:17050006"
FT MOD_RES 9
FT /note="Phosphoserine; by PKB/AKT1, RPS6KA3 and SGK3"
FT /evidence="ECO:0000269|PubMed:12054501,
FT ECO:0000269|PubMed:16484495, ECO:0000269|PubMed:20937854,
FT ECO:0000269|PubMed:24391509, ECO:0000269|PubMed:25169422,
FT ECO:0000269|PubMed:8250835"
FT MOD_RES 216
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:12554650,
FT ECO:0000269|PubMed:25169422"
FT MOD_RES 389
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9WV60"
FT MOD_RES 390
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 402
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT VAR_SEQ 303
FT /note="K -> KDSSGTGHFTSGVR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_004790"
FT MUTAGEN 9
FT /note="S->A: Loss of phosphorylation; abolished inhibition
FT of activity, leading to constitutively active."
FT /evidence="ECO:0000269|PubMed:17050006,
FT ECO:0000269|PubMed:28992046, ECO:0000269|PubMed:7980435"
FT MUTAGEN 85..86
FT /note="KK->AA: Abolished serine/threonine-protein kinase
FT activity."
FT /evidence="ECO:0000269|PubMed:17050006"
FT MUTAGEN 96
FT /note="R->A: Prevents the phosphorylation of phosphate-
FT primed glycogen synthase."
FT /evidence="ECO:0000269|PubMed:11430833"
FT MUTAGEN 128
FT /note="L->A: Abolishes activity toward AXIN1."
FT /evidence="ECO:0000269|PubMed:11430833"
FT CONFLICT 28
FT /note="V -> G (in Ref. 4; AAD48517)"
FT /evidence="ECO:0000305"
FT CONFLICT 350
FT /note="L -> H (in Ref. 1; AAA66475)"
FT /evidence="ECO:0000305"
FT STRAND 10..12
FT /evidence="ECO:0007829|PDB:2JDO"
FT STRAND 26..30
FT /evidence="ECO:0007829|PDB:1J1B"
FT STRAND 32..34
FT /evidence="ECO:0007829|PDB:4NM5"
FT STRAND 38..48
FT /evidence="ECO:0007829|PDB:1J1B"
FT STRAND 52..64
FT /evidence="ECO:0007829|PDB:1J1B"
FT STRAND 66..75
FT /evidence="ECO:0007829|PDB:1J1B"
FT TURN 76..78
FT /evidence="ECO:0007829|PDB:1J1B"
FT STRAND 81..88
FT /evidence="ECO:0007829|PDB:1J1B"
FT STRAND 91..93
FT /evidence="ECO:0007829|PDB:1Q5K"
FT HELIX 96..102
FT /evidence="ECO:0007829|PDB:1J1B"
FT STRAND 112..120
FT /evidence="ECO:0007829|PDB:1J1B"
FT TURN 121..124
FT /evidence="ECO:0007829|PDB:1J1B"
FT STRAND 125..133
FT /evidence="ECO:0007829|PDB:1J1B"
FT STRAND 136..138
FT /evidence="ECO:0007829|PDB:1Q5K"
FT HELIX 139..148
FT /evidence="ECO:0007829|PDB:1J1B"
FT HELIX 155..173
FT /evidence="ECO:0007829|PDB:1J1B"
FT TURN 174..176
FT /evidence="ECO:0007829|PDB:1J1B"
FT HELIX 184..186
FT /evidence="ECO:0007829|PDB:1J1B"
FT STRAND 187..190
FT /evidence="ECO:0007829|PDB:1J1B"
FT TURN 191..194
FT /evidence="ECO:0007829|PDB:1J1B"
FT STRAND 195..198
FT /evidence="ECO:0007829|PDB:1J1B"
FT HELIX 201..203
FT /evidence="ECO:0007829|PDB:5KPK"
FT STRAND 209..211
FT /evidence="ECO:0007829|PDB:6HK4"
FT HELIX 220..222
FT /evidence="ECO:0007829|PDB:4AFJ"
FT HELIX 225..228
FT /evidence="ECO:0007829|PDB:1J1B"
FT HELIX 237..252
FT /evidence="ECO:0007829|PDB:1J1B"
FT HELIX 262..273
FT /evidence="ECO:0007829|PDB:1J1B"
FT HELIX 278..284
FT /evidence="ECO:0007829|PDB:1J1B"
FT HELIX 286..288
FT /evidence="ECO:0007829|PDB:7B6F"
FT STRAND 289..291
FT /evidence="ECO:0007829|PDB:4ACC"
FT HELIX 301..304
FT /evidence="ECO:0007829|PDB:1J1B"
FT HELIX 311..320
FT /evidence="ECO:0007829|PDB:1J1B"
FT HELIX 325..327
FT /evidence="ECO:0007829|PDB:1J1B"
FT HELIX 331..335
FT /evidence="ECO:0007829|PDB:1J1B"
FT HELIX 338..344
FT /evidence="ECO:0007829|PDB:1J1B"
FT STRAND 345..347
FT /evidence="ECO:0007829|PDB:1UV5"
FT STRAND 353..355
FT /evidence="ECO:0007829|PDB:6HK4"
FT HELIX 364..367
FT /evidence="ECO:0007829|PDB:1J1B"
FT HELIX 371..373
FT /evidence="ECO:0007829|PDB:1J1B"
FT HELIX 374..377
FT /evidence="ECO:0007829|PDB:1J1B"
FT TURN 380..383
FT /evidence="ECO:0007829|PDB:1J1B"
SQ SEQUENCE 420 AA; 46744 MW; 4ACC24D00CDBB9C3 CRC64;
MSGRPRTTSF AESCKPVQQP SAFGSMKVSR DKDGSKVTTV VATPGQGPDR PQEVSYTDTK
VIGNGSFGVV YQAKLCDSGE LVAIKKVLQD KRFKNRELQI MRKLDHCNIV RLRYFFYSSG
EKKDEVYLNL VLDYVPETVY RVARHYSRAK QTLPVIYVKL YMYQLFRSLA YIHSFGICHR
DIKPQNLLLD PDTAVLKLCD FGSAKQLVRG EPNVSYICSR YYRAPELIFG ATDYTSSIDV
WSAGCVLAEL LLGQPIFPGD SGVDQLVEII KVLGTPTREQ IREMNPNYTE FKFPQIKAHP
WTKVFRPRTP PEAIALCSRL LEYTPTARLT PLEACAHSFF DELRDPNVKL PNGRDTPALF
NFTTQELSSN PPLATILIPP HARIQAAAST PTNATAASDA NTGDRGQTNN AASASASNST
